OP0051 LUPUS LOW DISEASE ACTIVITY STATE ATTAINMENT IN THE PHASE 3 PLACEBO-CONTROLLED TULIP LONG-TERM EXTENSION TRIAL OF ANIFROLUMAB
Authors: E. F. Morand, R. Van Vollenhoven, R. Furie, K. Kalunian, S. Yavuz, G. Abreu, C. Lindholm, H. Al-Mossawi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The Lupus Low Disease Activity State (LLDAS) has been prospectively validated as protective from flares, damage accrual, and mortality and is an important treatment goal in patients with SLE.<sup>[1]</sup> Recent analysis of pooled data from 2 phase 3 trials (TULIP-1 and TULIP-2) found that LLDAS attainment was achieved earlier, more frequently, and for a more sustained period with anifrolumab vs placebo in patients with moderate to severe SLE.<sup>[2]</sup> <h3>Objectives</h3> We investigated the long-term impact of anifrolumab compared with placebo on LLDAS attainment over the 1 year TULIP-1/TULIP-2 and 3 year long-term extension (LTE) study periods.<sup>[3]</sup> <h3>Methods</h3> TULIP-1 and TULIP-2 (NCT02446912, NCT02446899) were randomized, placebo-controlled, 52-week trials of IV anifrolumab (Q4W, 48 weeks) in patients with moderate to severe SLE despite standard therapy. Following the double-blind treatment period of the TULIP trials, patients could reconsent to participate in the 3-year, randomized, blinded, placebo-controlled LTE study (NCT02794285).<sup>[3]</sup> Here, data were analyzed by timepoint from TULIP baseline through the end of the LTE (Week 208) for patients who were assigned and received the same study drug (anifrolumab 300 mg or placebo) during the TULIP+LTE periods. LLDAS attainment was defined as all of the following: SLEDAI-2K ≤4 without major organ activity, no new disease activity, Physician's Global Assessment [0–3] ≤1, prednisone or equivalent ≤7.5 mg/day, standard immunosuppressant dosing, no use of restricted medications (considered only during the pooled TULIP-1/TULIP-2 period but not during the LTE period), and no investigational product (IP) discontinuation. LLDAS percentages and cumulative time in LLDAS were compared using a Cochran–Mantel–Haenszel approach, and response rates were compared using logistic regression. Last observation carried forward was used to impute missing data for TULIP-1/TULIP-2, but not for data captured in the LTE. All <i>P</i>-values are nominal. <h3>Results</h3> Data from 369 patients (anifrolumab 300 mg, n=257; placebo, n=112) were evaluable for the 4-year TULIP+LTE study period. At the last TULIP visit (Week 52), 39.3% of the anifrolumab group and 27.9% of the placebo group were in LLDAS (odds ratio [OR] 1.6, 95% CI 1.0–2.7, <i>P</i>=0.049). At the first visit of the LTE (Week 64), 33.5% of the anifrolumab group and 22.8% of the placebo group were in LLDAS (OR 1.7, 95% CI 1.0–2.9, <i>P</i>=0.038). LLDAS attainment was relatively stable for the first 3 years (up to Week 156) and declined slightly in Year 4; this decrease likely reflects the proportions of patients who discontinued IP over time (Figure 1). However, attainment of LLDAS favored anifrolumab vs placebo at all timepoints up to Week 208 (OR 2.7, 95% CI 1.3–5.6, <i>P</i>=0.007). For the combined 4-year TULIP+LTE period, greater cumulative time (<i>P</i>=0.001) and percentage of time (<i>P</i>=0.006) was spent in LLDAS by patients receiving anifrolumab compared with placebo. Cumulative time in LLDAS at a threshold of ≥20% also favored anifrolumab (OR 2.2, 95% CI 1.4–3.5, <i>P</i>=0.001); a similar trend was seen with a threshold of ≥50%, although this did not reach statistical significance (OR 1.4, 95% CI 0.8–2.4, <i>P</i>=0.217). Compared with placebo, patients treated with anifrolumab were more likely to be in sustained LLDAS for ≥3 consecutive visits (49.4% vs 35.1%; OR 1.8, 95% CI 1.1–2.8, <i>P</i>=0.018), ≥5 consecutive visits (32.6% vs 20.1%; OR 1.8, 95% CI 1.0–3.1, <i>P</i>=0.033), or ≥7 consecutive visits (22.2% vs 11.6%; OR 2.1, 95% CI 1.1–4.1, <i>P</i>=0.028). <h3>Conclusion</h3> Anifrolumab 300 mg treatment was associated with more frequent, prolonged, and sustained LLDAS compared with placebo during the 4-year TULIP+LTE period. <h3>References</h3> [1]Golder V, et al. <i>Lancet Rheumatol.</i> 2019;1:e95–102. [2]Morand E. <i>Arthritis Rheumatol.</i> 2021;73 (suppl 9). [3]Kalunian KC, et al. <i>Arthritis Rheumatol</i> 2022. doi: 10.1002/art.42392 <h3>Acknowledgements</h3> Writing assistance by Jack Barton, PhD, and Rosie Butler, PhD, of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca. <h3>Disclosure of Interests</h3> Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, Janssen, Pfizer, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Pfizer, Sanofi, UCB, Grant/research support from: AstraZeneca, BMS, GSK, Lilly, Pfizer, Roche, UCB, Richard Furie Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Kenneth Kalunian Consultant of: Biogen, AstraZeneca, BMS, Genentech/Roche, Amgen, Equilliumbio, Kezarbio, GSK, Merck, Abbvie, Grant/research support from: UCB, Novartis, Amgen, Lupus Foundation of America, Lupus Research Alliance, NIH, Sule Yavuz Employee of: AstraZeneca, Gabriel Abreu Employee of: AstraZeneca, Catharina Lindholm Shareholder of: AstraZeneca, Employee of: AstraZeneca, Hussein Al-Mossawi Shareholder of: AstraZeneca, UCB, GSK, Speakers bureau: Novartis, Pfizer, UCB, Consultant of: Novartis, UCB, Abbvie, Grant/research support from: UCB, Employee of: UCB (Previous), AstraZeneca (Current)